ORIGINAL ARTICLE

The Genetic Epidemiology of Irrational Fears

and Phobias in Men
Kenneth S. Kendler, MD; John Myers, MS; Carol A. Prescott, PhD; Michael C. Neale, PhD

Background: Much of our knowledge of the role of ge-
netic factors in the etiology of phobias comes from one
population-based sample of female twins. We examined
the sources of individual differences in the risks for pho-
bias and their associated irrational fears in male twins.
Methods: In personal interviews with both members of
1198 male-male twin pairs (707 monozygotic [MZ] and
491 dizygotic [DZ]) ascertained from a population-
based registry, we assessed the lifetime history of agora-
phobia and social, animal, situational, and blood/injury
phobias as well as their associated irrational fears. Twin
resemblance was assessed by means of probandwise con-
cordance, odds ratios, tetrachoric correlations, and uni-
variate and multivariate biometrical model fitting.
phobias. All 5 phobia subtypes aggregate within twin-
pairs. This aggregation is due largely or solely to genetic
factors with heritability of liabilities ranging from 25%
to 37%. Multivariate analysis revealed a common ge-
netic factor, genetic factors specific to each subtype, and
a common familial-environmental factor.
Conclusions: In male subjects, genetic risk factors,
which are partially common across all subtypes and
partially subtype specific, play a moderate role in the
etiology of phobias and their associated irrational fears.
Family environment probably has an impact on risk for
agoraphobia and social phobia. The genetic liability to
blood/injury phobias is not distinct from those of the
more typical phobias.

Results: The suggestive results obtained by analysis of

phobias only were supported by analyzing both fears and Arch Gen Psychiatry. 2001;58:257-265

From the Virginia Institute for
Psychiatric and Behavioral
Genetics (Drs Kendler,
Prescott, and Neale and
Mr Myers) and the
Departments of Psychiatry
(Drs Kendler, Prescott, and
Neale and Mr Myers) and
Human Genetics (Drs Kendler
and Neale), Medical College
of Virginia of Virginia
Commonwealth University,
Richmond.
F
AMILY STUDIES suggest that
phobias are familial,1-6 but
cannot clarify the origin of
this family resemblance. Twin
studies of self-reported fears
consistently have suggested a significant role
for genetic factors.7-11 By contrast, twin stud-
ies of clinically defined phobias have, with
one exception, suffered from very small
samples sizes with resultant low power to
discriminate alternative models of familial
transmission.12-14 This exception is our pre-
vious study of phobias in female-female
twins from the Virginia Twin Registry.15-17
These reports examined 5 types of pho-
bias—agoraphobia (AgP), social phobia
(SoP), animal phobia (AnP), situational pho-
bia (SiP), and blood/injury phobia (BiP)—
and reached the following conclusions. First,
all phobia subtypes are moderately famil-
ial. Second, familial aggregation of AgP, SoP,
and AnP is due to genetic factors. For SiP
and BiP, results based on our first assess-
ment15,16 suggested that twin resemblance
might result from familial-environmental
factors. However, when our analyses in-
cluded a second assessment interview,17 the
added power obtained through control of
measurement error suggested that the re-
sults for these phobia subtypes were simi-
lar to those for the others (ie, the familial
transmission due solely to genetic factors).
Third, high levels of comorbidity were seen
between the phobia subtypes.15 Contrary to
results from family studies,4 the best-
fitting multivariate model suggested com-
mon genetic and individual-specific envi-
ronmental factors that influenced risk for
all phobia subtypes, as well as genetic and
environmental factors unique to each sub-
type. However, these analyses did not in-
clude BiP, which was assessed at a later wave.
Blood/injury phobia differs from typical pho-
bias,18 where exposure to phobic stimuli (eg,
snakes, heights, and public speaking) usu-
ally produces increased sympathetic activ-
ity (eg, tachycardia, increased blood pres-
sure, sweating, and flushing). By contrast,
in individuals with BiP, exposure to pho-
bic stimuli (eg, needles and blood) usually
increases parasympathetic activity (eg, bra-
dycardia, hypotension, pallor, and fainting).
Given these differences, would the genetic
and environmental risk factors for BiP be dis-
tinct from those for the other phobia sub-
types?

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 SUBJECTS AND METHODS
SAMPLE AND ASSESSMENT PROCEDURES
This report is based on data from the second wave of in-
terviews in our study of adult twins from the Virginia Twin
Registry (now part of the Mid-Atlantic Twin Registry), de-
tails of which have been outlined previously.19 Briefly, twins
were eligible for participation if one or both members were
successfully matched and if they were white, a member of
a multiple birth that included at least 1 male, and born be-
tween 1940 and 1974. Of 9417 eligible individuals for the
first wave, 6814 (72.4%) completed initial interviews. For
those who completed the initial interview, we recontacted
them to schedule a second interview at least 1 year later.
Where possible, this interview was completed face-to-face
(79.4% of sample). Of the eligible individuals, 5629 (82.6%)
were successfully interviewed. To assess test-retest reli-
ability, 150 members of male-male twins were reinter-
viewed a mean (± SD) of 4.4±1.1 weeks after their initial
interview.
The current report is based on 1198 male-male pairs
(707 monozygotic [MZ] and 491 dizygotic [DZ]) with com-
plete data on irrational fears and phobias from the second-
wave interview and 544 interviewed individual twins (254
from MZ and 290 from DZ pairs) with complete data whose
co-twins did not complete a second-wave interview.
At the second-wave interview (1994 through 1998),
subjects were aged 20 to 58 years (mean ± SD, 36.8 ± 9.1
years). Interviewers had a master’s degree in a mental health–
related field or a bachelor’s degree in this area plus 2 years
of clinical experience. Members of a twin pair were in-
terviewed by different interviewers unaware of clinical
information about the co-twin. Zygosity diagnosis was
In this report, using our recently studied sample of
male-male twin pairs ascertained from the same regis-
try, we address the following questions:
1. What are the sources of individual differences in
risk for the 5 phobia subtypes in male twins?
2. Do irrational fears without impairment reflect a
milder form of the same liability dimensions as classic
phobias? If so, will including such fears in the modeling
improve power and the ability to discriminate compet-
ing models?
3. What is the level of comorbidity among individual
phobia subtypes in this population sample? To what degree
do genetic and environmental common factors contribute
to the observed patterns of comorbidity, and will these com-
mon factors have less impact on the liability to BiP than on
the liability to the more typical phobia subtypes?
RESULTS
TEST FOR BIASES AND RELIABILITY
We performed 12 analyses predicting twin concordance
for each phobia subtype and any phobias from the simi-
larity of their childhood environment and the frequency
of adult contact. Three were significant at the 5% level; 2,
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performed using a discriminant function analysis based on
6 standard zygosity questions. The algorithm was devel-
oped on 227 twin pairs who underwent genotyping using
8 or more highly polymorphic DNA markers.19
We assessed a lifetime history of phobias with an ad-
aptation of the phobic disorders section of the Diagnostic
Interview Schedule (DIS) Version III-A.15,20 The 22 specific
individual fears that were assessed are outlined in Table 1.
We also asked respondents “Is there anything else you’ve been
unreasonably terrified to do or be near?” If any phobia de-
scribed in response to this question best belonged with 1 of
the 5 specific subtypes, it was so treated. Other phobias men-
tioned in response to this question (eg, fear of darkness) were
included in our analysis of any phobia, but were not counted
as belonging to a specific subtype.
In the DIS, to be considered a phobia, the fear must
result in seeing a physician, taking medications, or report-
ing that the fear or its avoidance “interfered with life or ac-
tivities a lot.” Given the low and variable rates of treat-
ment seeking for phobias,21 we defined phobias solely
through a modification of the third criterion, objective im-
pact of the fear on respondent behavior. In contrast to the
DIS, where the respondent makes the judgment about fear-
associated interference, in our interview, the interviewer
made this assessment.
STATISTICAL ANALYSIS
The univariate and multivariate twin models used in this
report are described elsewhere.15,22 We assume that varia-
tion in liability to phobias results from the following 3 sets
of factors: (1) additive genetic (A), which contribute twice
as much to the correlation in MZ twins as DZ twins; (2)
family or common environment (those familial factors such
in the direction opposite that predicted. Controlling for
zygosity, twin pairs with more similar childhood environ-
ments were significantly less likely to be concordant for
AnP (x21 =5.55; P=.02) and SiP (x21 =4.10; P=.04). Those
in frequent adult contact were significantly more likely to
be concordant for SiP (x21 =5.27; P=.02).
Short-term test-retest reliability for irrational fears and
phobias, as assessed by the coefficient and the tetrachoric
correlation, were modest to moderate (Table 2). With the
exception of social fears/SoP, irrational fears were more re-
liably reported than phobias. The reliability of the assign-
ment of a phobia given an irrational fear was particularly
modest. Consistent with our previous results,17 individu-
als may be more reliable at recalling irrational fears than
they are at reporting their behavioral consequences.
DESCRIPTION BY INDIVIDUAL FEAR
Many more individuals endorsed an irrational fear than
met criteria for an associated phobia (Table 1). How-
ever, this ratio differed widely. For example, although
46% of individuals who feared being in crowds met cri-
teria for AgP, the parallel figures for fears of needles, giv-
ing a speech, and snakes were 18%, 15%, and 14%, re-
spectively. Table 1 also presents, within each of the phobia
subtypes, the proportion of individuals who met crite-
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 as parental attitudes that are shared by members of a twin
pair) (C), which contribute equally to the correlation in
MZ and DZ twins; and (3) individual specific environ-
ment (E), which reflect environmental experiences not
shared by members of a twin pair and therefore contribute
to differences between them in their phobia histories.
Our multivariate twin analyses decompose into ge-
netic and environmental sources the variance in phobia li-
ability and the covariance in liability among different pho-
bia subtypes. We attempt, in these analyses, to explain the
correlations between the phobia subtypes as resulting from
a small number of latent factors. Multivariate genetic analy-
sis goes beyond traditional factor analysis in providing in-
sight into the causes of resemblance among variables.
Two alternative multivariate models that describe how
genetic and environmental factors influence covariation are
tested. Genetic and environmental factors could influence
covariation through a single common pathway.23 By con-
trast, in the independent pathway model, genes and the
environment contribute to covariation through separate
genetic and environmental latent factors.
Having 5 phobia subtypes, two factors were poten-
tially identifiable. However, we focused on single com-
mon factor models, because this was the approach used
previously.15 The relationship between the common ge-
netic factor and BiP was evaluated by setting the connect-
ing path to 0 and examining the change in fit.
To use complete twin pairs and twins whose co-twin
was not interviewed, we used an Mx option24 to fit models
by maximum likelihood. During optimization, trial values
of the parameters are used to generate a predicted covari-
ance matrix and a matrix of thresholds. For any particular
observation, the overall matrix is filtered to create a sub-
matrix matching those observations that are present.
ria for phobia based on each specific fear. The most com-
mon impairing fears for each subtype were being in crowds
for AgP, giving a speech for SoP, snakes for AnP, other
high places for SiP, and dentists or hospitals for BiP.
The most common phobia subtype was SiP, fol-
lowed by SoP, BiP, AnP, and AgP. No significant differ-
ences were seen in the prevalence of the phobia subtypes
or any phobia in MZ vs DZ twins (results not shown).
TWIN RESEMBLANCE
Twin resemblance was seen for all 5 of the phobia sub-
types in MZ twins, with the odds ratios (ORs) ranging
from 2.30 for SoP to 4.64 for AnP (Table 3). In DZ twins,
twin resemblance was seen for AgP, SoP, and AnP, but
not for SiP or BiP. For all phobia subtypes as well as for
any phobia, the OR and tetrachoric correlations in MZ
twins exceeded those seen in DZ twins, suggesting the
importance of genetic risk factors.
UNIVARIATE MODEL FITTING
TO PHOBIAS ONLY
Table 4 shows the results of model fitting for each of
the phobia subtypes and for any phobia. For AgP and SoP,
the full ACE model suggested that twin resemblance re-
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Likewise, the corresponding subset of the matrix of thresh-
olds is created. These matrices are then used to compute
the log-likelihood of the observation in question. The log-
likelihoods of all cases are summed to obtain the log-
likelihood of the sample, which is maximized using nu-
merical optimization software. An advantage of this method
is that it reduces the possible impact of cooperation bias
by using information on potential differences in the preva-
lence of phobias in those twins with vs those without a co-
twin participating to obtain a better estimate of true preva-
lences.
Because maximum likelihood analysis of raw ordinal
data does not provide an overall test of goodness of fit, we
compare relative fits against the full model. Twice the dif-
ference in log-likelihood between the full model and sub-
model tested yields a statistic that is asymptotically x2, with
degrees of freedom equal to the difference in the number
of parameters in both models. Alternative models are evalu-
ated for the optimal balance between explanatory power
and parsimony, which is operationalized by Akaike’s In-
formation Criterion (AIC).25,26
Because unreasonable fears are more common than
phobias, analysis including fears would have increased
power.27 Such analysis would be appropriate if fears and
phobias resulted from a single continuum of liability, a hy-
pothesis testable by the multiple-threshold model.28 For our
analyses, P indicates phobias only, and FP, fears and pho-
bias.
We tested the equal environment assumption that
exposure of MZ and DZ twin pairs to environmental risk
factors for fears and phobias was equally correlated by pre-
dicting twin concordance for phobias, controlling for
zygosity by means of the similarity of environmental ex-
periences of the twins in childhood29 and adulthood.
sulted from both genetic and familial-environmental fac-
tors. When we tested the simpler AE and CE models in
these 2 phobias, they produced nearly identical fits. Table
4 presents results for the AE model. The CE model pro-
duced the following estimates for c2 and e2: −0.29 and
0.71, respectively, for AgP, and 0.17 and 0.83, respec-
tively, for SoP. The E-only model, by contrast, fit more
poorly for both phobias. Although AgP and SoP aggre-
gated within twin pairs, we had no power to distinguish
the degree to which this was due to genetic and/or en-
vironmental mechanisms.
For AnP, SiP, BiP, and any phobia, c2 was esti-
mated at 0 in the full model, indicating that twin resem-
blance was ascribed entirely to genetic factors. In each
case, the AE model fit somewhat better than the CE
model, with estimates of heritability ranging from 0.22
(for any phobia) to 0.35 (for AnP). The very wide confi-
dence intervals (CIs) on these heritability estimates are
noteworthy. Furthermore, using the more rigorous x2
difference test, we could not reject the CE against the
ACE model at any level approaching statistical signifi-
cance. Indeed, even the test for familial aggregation of
phobias (the ACE vs E-only model) was significant only
for AgP (x22 =6.05; P=.05), AnP (x22 =6.65; P=.04), SiP
(x 2 2 = 7.02; P = .03), and any phobia (x 2 2 = 10.83;
P=.004).
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 suggested for all 5 phobia subtypes that the familial ag-
Table 1. Specific Irrational Fears and Phobias gregation of phobia susceptibility was due solely to ge-
in 2940 Male Twins* netic factors. For each phobia/fear, AE was the best-fit
model, with estimates of the heritability of liability rang-
% of Sample (±SE)
Phobia, % of ing from 0.24 for SoFP to 0.43 for AgFP. Second, the sta-
Subtype, Item Irrational Fear Phobia Subtype ± SE tistical power with which we could reject alternative mod-
Agoraphobia els was substantially greater. Using the x2 difference test,
Going out of house alone 1.6 ± 0.2 0.6 ± 0.1 15.3 ± 3.3 we could reject the CE model against the ACE model at
Being in crowds 7.2 ± 0.5 3.3 ± 0.3 83.1 ± 3.5 or near the 5% level for the following 4 of the 5 fear/
Being in open spaces 0.4 ± 0.1 0.3 ± 0.1 8.5 ± 2.6 phobia subtypes: AgFP (x 2 1 = 3.64; P = .06), AnFP
1 or more items 8.6 ± 0.5 4.0 ± 0.4 100.0
(x21 =11.87; P,.001), SiFP (x21 =8.09; P=.004), and BiFP
Social phobia
Meeting new people 5.3 ± 0.4 1.4 ± 0.2 21.6 ± 3.0
(x21 = 3.21; P = .07). For all fears/phobias, we could re-
Giving a speech 29.5 ± 0.8 4.4 ± 0.4 70.7 ± 3.4 ject the E only (or no familial transmission model) with
Using public bathrooms 4.4 ± 0.4 1.3 ± 0.2 20.1 ± 3.0 confidence, ie, AgFP (x 2 2 = 21.49; P,.001), SoFP
Eating in public 1.4 ± 0.2 0.6 ± 0.2 10.3 ± 2.2 (x22 =22.97; P,.001), AnFP (x22 =42.17; P,.001), SiFP
1 or more items 32.7 ± 0.9 6.3 ± 0.5 100.0 (x22 = 34.32; P,.001), and BiFP (x22 = 25.30; P,.001).
Animal phobia Third, the CIs around the parameter estimates were con-
Spiders 7.9 ± 0.5 1.1 ± 0.2 21.7 ± 3.3
Bugs 2.5 ± 0.3 0.4 ± 0.1 8.6 ± 2.3
siderably narrower when we considered both fears and
Mice 1.6 ± 0.2 0.2 ± 0.1 3.3 ± 1.5 phobias in the model fitting compared with phobias alone.
Snakes 20.0 ± 0.7 2.9 ± 0.3 55.9 ± 4.0
Bats 2.2 ± 0.3 0.2 ± 0.1 4.6 ± 1.7 COMORBIDITY AMONG PHOBIA SUBTYPES
Other animals 3.9 ± 0.4 1.2 ± 0.2 23.0 ± 3.4 AND MULTIVARIATE MODEL FITTING
1 or more items 28.3 ± 0.8 5.2 ± 0.4 100.0
Situational phobia
Substantial comorbidity exists among all combinations
Tunnels 3.5 ± 0.3 0.5 ± 0.1 5.8 ± 1.4
Other closed places 9.1 ± 0.5 2.3 ± 0.3 24.3 ± 2.6 of the phobia subtypes (Table 6). As measured by OR
Bridges 4.1 ± 0.4 0.9 ± 0.2 9.1 ± 1.7 or tetrachoric correlations, the highest comorbidity is seen
Airplanes 8.0 ± 0.5 2.0 ± 0.3 21.4 ± 2.5 between AgP and SoP, followed by SoP and BiP. The pat-
Other high places 18.3 ± 0.7 4.8 ± 0.4 50.4 ± 3.0 tern of comorbidity of BiP is similar to that seen with more
1 or more items 31.2 ± 0.9 9.4 ± 0.5 100.0 “typical” phobias.
Blood/injury phobia
Because of greater statistical power and stability of
Sight of blood 4.4 ± 0.4 0.6 ± 0.2 11.3 ± 2.4
Needles or injections 11.1 ± 0.6 2.0 ± 0.3 34.5 ± 3.7
estimates, we performed multivariate model fitting with
Dentists or hospitals 6.9 ± 0.5 2.5 ± 0.3 43.7 ± 3.8 fears and phobias, the results of which are outlined in
Certain diseases such 9.4 ± 0.5 1.6 ± 0.2 27.4 ± 3.4 Table 7. Model 1 was the full independent pathway
as AIDs or cancer model with the A, C, and E common factors as well as
1 or more items 23.3 ± 0.8 5.7 ± 0.4 100.0 the A, C, and E factors specific to each phobia subtype.
When we tried to simplify this to a common pathway
*AIDS indicates acquired immunodeficiency syndrome.
model, the fit deteriorated substantially, and the AIC in-
creased. Therefore, in subsequent models, we set to 0,
UNIVARIATE MODEL FITTING in turn, the C common factor (model 3), the A common
TO FEARS AND PHOBIAS factor (model 4), the E common factor (model 5), the
phobia-specific C paths (model 6), and the phobia-
We began by testing with the multiple threshold model28 specific A paths (model 7). The AIC improved only for
the assumption that irrational fears and phobias repre- model 6. Indeed, the fit of the model was unchanged when
sented differing points on a single continuum of liabil- constraining to zero C paths unique to each phobia.
ity. Although none of the results for the 5 phobia sub- We then tested the relationship between the ge-
types, examined separately in MZ and DZ twins, were netic risk factors for BiFP and the more typical phobias.
statistically significant, the results for any phobia were Starting with model 6, we constrained to 0 the path from
significant in both twin groups (MZ, x25 = 80.0; P,.001; the common genetic factor to BiFP, thereby forcing all
DZ, x25 =67.7; P,.001). Therefore, we proceeded with genetic risk for BiFP to be independent of the other pho-
model fitting using the trivariate classification of unaf- bia subtypes. This model fit substantially more poorly than
fected, fear only, and phobia for the 5 specific subtypes model 6, with a deterioration of 6.5 x2 units (P=.01).
of fears and phobias only. The test-retest reliability for Parameter estimates for the best-fit model 6 are
this trichotomy is shown in Table 2. seen in the Figure and Table 8. Five results are note-
The magnitude of the polychoric correlations for worthy. First, contrary to the hypothesis that the
fears/phobias in MZ and DZ twins (Table 3) are gener- genetic risk factors for BiFP are distinct from those for
ally similar to those seen with phobias only (although the more typical phobias, BiFP actually had the highest
there are some exceptions, eg, AgP). However, as ex- loading on the common genetic factor. Second, the
pected, the SEs of these correlations are substantially best-fit model also contained genetic risk factors spe-
smaller than those seen with phobias alone. cific to each phobia subtype. These genetic-specific fac-
The pattern of modeling results for fears and pho- tors were most important for SoFP, AnFP, and SiFP.
bias (Table 5) differed from that found with phobias Third, unlike the univariate analysis for fears/phobias
alone in 3 important ways. First, the full or ACE model (but more like the univariate analyses for phobias

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 Table 2. Test-Retest Reliability of Irrational Fears, Phobias, and Phobias for 150 Subjects Who Admit to Fears*

Phobia
Fear† Phobia† Fear-Phobia Dimension‡ (for Those Having Fear)†§

Tetrachoric Tetrachoric Polychoric Tetrachoric

Subtype k Correlation k Correlation Weighted k Correlation k Correlation
Agoraphobia 0.56 (0.28-0.85) 0.88 (0.60-0.98) 0.27 (−0.17-0.71) 0.72 (0.04-0.97) 0.48 (0.23-0.73) 0.86 (0.60-0.96) ... ...
Social phobia 0.35 (0.20-0.51) 0.60 (0.36-0.78) 0.37 (0.05-0.69) 0.76 (0.34-0.95) 0.36 (0.21-0.51) 0.64 (0.44-0.79) 0.31 (−0.12-0.74) 0.51 (−0.20-0.90)
Animal 0.58 (0.44-0.71) 0.80 (0.65-0.90) 0.17 (−0.09-0.44) 0.43 (−0.07-0.79) 0.50 (0.37-0.62) 0.70 (0.54-0.82) 0.14 (−0.20-0.48) 0.29 (−0.35-0.78)
phobia
Situational 0.58 (0.44-0.73) 0.82 (0.66-0.91) 0.35 (0.09-0.60) 0.66 (0.31-0.88) 0.52 (0.40-0.64) 0.78 (0.64-0.88) 0.16 (−0.19-0.51) 0.26 (−0.31-0.71)
phobia
Blood/injury 0.60 (0.45-0.76) 0.84 (0.67-0.93) 0.21 (−0.08-0.50) 0.50 (−0.01-0.83) 0.51 (0.37-0.65) 0.76 (0.59-0.87) 0.08 (−0.35-0.52) 0.15 (−0.53-0.74)
phobia
Any phobia 0.51 (0.37-0.66) 0.76 (0.59-0.87) 0.36 (0.18-0.53) 0.58 (0.33-0.77) 0.45 (0.33-0.56) 0.67 (0.52-0.78) 0.30 (0.08-0.51) 0.46 (0.12-0.72)

*Parenthetical data are 95% confidence intervals.

†Zero indicates none; 1, fear.
‡Zero indicates none; 1, fear; and 2, phobia.
§For agoraphobia, sample was too small for stable estimate.

Table 3. Prevalence and Measures of Similarity for Phobias in MZ and DZ Male-Male Twin Pairs*

MZ Pairs (707 Pairs) DZ Pairs (491 Pairs)

Fears and Fears and

Phobias Phobias Phobias Phobias
Tetrachoric Polychoric Tetrachoric Polychoric
Probandwise Odds Ratio Correlation Correlation Probandwise Odds Ratio Correlation Correlation
Phobia Prevalence Concordance (95% CI) (ASE) (ASE) Prevalence Concordance (95% CI) (ASE) (ASE)
Agoraphobia 0.035 0.122 4.29 0.320 (0.157) 0.435 (0.089) 0.050 0.122 2.93 0.252 (0.166) 0.169 (0.122)
(1.19-15.47) (0.81-10.58)
Social 0.067 0.126 2.30 0.208 (0.124) 0.249 (0.055) 0.062 0.098 1.73 0.132 (0.161) 0.129 (0.069)
(0.92-5.77) (0.50-6.07)
Animal 0.045 0.159 4.64 0.360 (0.133) 0.397 (0.053) 0.053 0.077 1.58 0.103 (0.181) 0.037 (0.075)
(1.65-13.01) (0.35-7.08)
Situational 0.093 0.212 3.09 0.314 (0.096) 0.343 (0.053) 0.095 0.065 0.64 −0.109 (0.143) 0.055 (0.068)
(1.60-5.96) (0.19-2.15)
Blood/injury 0.054 0.156 3.62 0.314 (0.125) 0.309 (0.061) 0.100 0.041 0.81 −0.043 (0.210) 0.120 (0.079)
(1.42-9.27) (0.11-6.27)
Any 0.217 0.313 1.93 0.224 (0.070) . . .† 0.209 0.244 1.30 0.087 (0.089) . . .†
(1.29-2.89) (0.77-2.17)

*MZ indicates monozygotic; DZ, dizygotic; CI, confidence interval; and ASE, asymptotic SE.
†Ellipses indicate results were not presented because multiple threshold model fit poorly.

alone), we found evidence of the impact of shared envi-
ronment, but only in the form of a common factor. This
common factor significantly affected only AgFP and
SoFP. Fourth, the best-fit model contained one com-
mon E factor. That is, some environmental experiences
that were unique to individual twins influence the gen-
eral risk for fears/phobias. This factor had highest load-
ings on AgFP and SoFP. Finally, substantial specific E
loadings were seen for all subtypes, which would repre-
sent an admixture of measurement error and environ-
mental experiences that predisposed uniquely to indi-
vidual phobia subtypes.
COMMENT
We addressed 3 questions about the genetic epidemiol-
ogy of irrational fears and phobias in male-male twin pairs
from a population-based registry. We examine these ques-
tions in turn.
Individual phobia subtypes and any phobia aggre-
gated within twin pairs. For AnP, SiP, BiP, and any pho-
bia, the best-fit model suggested that familial aggrega-
tion was due solely to genetic factors with modest
heritabilities. For AgP and SoP, model fitting could not
distinguish between genetic and familial-environmen-
tal sources of twin resemblance. For all the phobia sub-
types, power was limited, and CIs for the parameter es-
timates were broad.
Many twins in our sample reported irrational fears
without objective impact on their lives. Given our need
for greater statistical power to resolve sources of indi-
vidual differences and the low reliability with which in-
dividuals recalled whether the fears were impairing, we
applied the multiple-threshold model28 to a trichoto-
mous classification of all individuals into unaffected, fear
only, and phobia. Results from these analyses indicated
that for all the phobia subtypes, the pattern of results
within MZ and DZ twins pairs were consistent with the

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 Table 4. Model-Fitting Results for Phobias in Male-Male Twin Pairs*

Parameter Estimates

Fit of Models† Full Best-Fit

Phobia ACE AE CE E a2 c2 e2 a2 95% CI e2 95% CI

Agoraphobia‡
x2 984.0 984.2 984.2 990.1 0.20 0.14 0.66 0.37 0.07-0.61 0.63 0.39-0.93
AIC ... −1.8§ −1.8§ 2.1 ... ... ... ... ... ... ...
Social‡
x2 1383.9 1383.9 1383.9 1386.9 0.11 0.08 0.81 0.20 0.00-0.41 0.80 0.59-1.00
AIC ... −2.0§ −2.0§ −1.0 ... ... ... ... ... ... ...
Animal
x2 1189.8 1189.8 1191.1 1196.4 0.35 0.00 0.65 0.35 0.09-0.58 0.65 0.42-0.91
AIC ... −2.0§ −0.7 2.6 ... ... ... ... ... ... ...
Situational
x2 1837.5 1837.5 1840.3 1844.5 0.25 0.00 0.75 0.25 0.07-0.43 0.75 0.57-0.93
AIC ... −2.0§ 0.8 3.0 ... ... ... ... ... ... ...
Blood/injury
x2 1282.8 1282.8 1284.2 1287.8 0.28 0.00 0.72 0.28 0.03-0.51 0.72 0.49-0.97
AIC ... −2.0§ −0.6 1.0 ... ... ... ... ... ... ...
Any
x2 3080.3 3080.3 3081.7 3091.1 0.22 0.00 0.78 0.22 0.09-0.34 0.78 0.66-0.91
AIC ... −2.0§ −0.6 6.8 ... ... ... ... ... ... ...

*A indicates additive genetic factors; C, family or common environment factors; E, individual specific environment factors; CI, confidence interval; and AIC,
Akaike’s Information Criterion.25 Analyses were based on 1198 complete twin pairs and 544 single twins.
†Degrees of freedom were 2937 for ACE, 2938 for AE and CE, and 2939 for E.
‡For these phobias, we present parameters from the AE model as the best fit, but the CE model also fit nearly as well, results of which are presented in the
“Univariate Model Fitting to Phobias Only” subsection of the “Results” section.
§Best-fit models by means of AIC.

Table 5. Model-Fitting Results for Fears and Phobias in Male-Male Twin Pairs*

Parameter Estimates

Fit of Models† Full Best-Fit

Phobia ACE AE CE E a2 c2 e2 a2 95% CI e2 95% CI

Agoraphobia
x2 2040.8 2040.8 2044.4 2062.3 0.43 0.00 0.57 0.43 0.26-0.59 0.57 0.41-0.74
AIC ... −2.0† 1.6 17.5 ... ... ... ... ... ... ...
Social
x2 4637.2 4637.2 4638.9 4660.1 0.24 0.00 0.76 0.24 0.15-0.34 0.76 0.66-0.85
AIC ... −2.0† −0.3 18.9 ... ... ... ... ... ... ...
Animal
x2 4249.1 4249.1 4261.0 4291.3 0.37 0.00 0.63 0.37 0.26-0.47 0.63 0.53-0.74
AIC ... −2.0† 9.9 38.2 ... ... ... ... ... ... ...
Situational
x2 4745.6 4745.6 4753.7 4779.9 0.31 0.00 0.69 0.31 0.21-0.40 0.69 0.60-0.79
AIC ... −2.0† 6.1 30.3 ... ... ... ... ... ... ...
Blood/injury
x2 3926.5 3926.5 3929.7 3951.8 0.30 0.00 0.70 0.30 0.19-0.41 0.70 0.59-0.81
AIC ... −2.0† 1.2 25.3 ... ... ... ... ... ... ...

*Abbreviations and degrees of freedom for fit of models are given in the first and second footnotes to Table 4. Analyses were based on 1198 complete twin
pairs and 544 single twins. Degrees of freedom for fit of models were as follows: ACE, 2936; AE, 2937; CE, 2937; and E, 2938.
†Best fit model(s) by means of AIC.25

hypothesis that fears were a milder manifestation of the
same liability dimension that produced clinical pho-
bias. We found similar results in our female twins.17
We repeated our analysis using this trichotomous
classification, with results that were substantially clearer
than those obtained for phobias alone. With the in-
creased statistical power, evidence of familial-environ-
mental effects on AgP and SoP disappeared. The
best-fit model for all the phobia subtypes suggested that
familial resemblance was due solely to genetic factors, again
with modest heritability estimates, but now with consid-
erably smaller CIs.
We recently fitted multiple threshold models to data
on fears and phobias from the previously studied female-
female pairs17 to which our current results can be com-
pared usefully. We used a measurement model based on

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 Table 6. Tetrachoric Correlation and Odds Ratios Between Phobias*

Phobia Agoraphobia Social Phobia Animal Phobia Situational Phobia Blood/Injury Phobia
Agoraphobia 12.78 (8.51-19.18) 5.37 (3.32-8.70) 3.70 (2.40-5.68) 3.44 (2.05-5.78)
Social 0.61 (0.05) 4.59 (3.01-7.01) 3.83 (2.68-5.46) 5.89 (3.99-8.70)
Animal 0.40 (0.06) 0.38 (0.06) 3.81 (2.59-5.59) 5.20 (3.39-7.96)
Situational 0.33 (0.06) 0.36 (0.05) 0.35 (0.05) 4.40 (3.07-6.31)
Blood/injury 0.29 (0.07) 0.45 (0.05) 0.41 (0.06) 0.39 (0.05)

*Data in lower-left triangle are given as tetrachoric correlations (asymptotic SE); in upper-right triangle, odds ratios (95% confidence intervals).

Table 7. Multivariate Model-Fitting Results for Specific Fears/Phobias*

Model Fear/Phobia Common Factors Fear/Phobia Specific Factors Pathway x2 df AIC†

1 ACE ACE Independent 18 675.7 14 662 . . .‡
2 ACE ACE Common 18 714.9 14 671 21.2
3 AE ACE Independent 18 690.3 14 667 5.6
4 CE ACE Independent 18 703.3 14 667 17.6
5 AC ACE Independent 18 836.5 14 667 150.8
6 ACE AE Independent 18 675.7 14 667 −10.0
7 ACE CE Independent 18 686.9 14 667 1.2

*Abbreviations are given in the first footnote to Table 4.

†Explained in Akaike.25
‡No estimate of AIC possible for first or full model.

2 waves of interviews from which we can derive ex-

pected heritability from a single interview: for AgFP, 0.47; AC CC EC

for SoFP, 0.31; for AnFP, 0.27; for SiFP, 0.26; and for 0.47 0.48 – 0.12 0.50
BiFP, 0.32. These results, well within the 95% CIs ob- 0.36 0.22 0.03 0.65
tained in the male sample, suggest that the role of ge- 0.46 – 0.03 0.38
0.33 0.22 0.34 0.46
netic factors in liability to irrational fears and phobias are
probably similar in men and women.
Similar to other community samples,15,30 substan-
tial comorbidity was seen between phobia subtypes. Mul-
tivariate twin modeling is a powerful method to exam- Agoraphobia Social Animal Situational Blood/Injury
ine the contributions of genetic and environmental factors Phobia Phobia Phobia Phobia

to observed patterns of comorbidity. Given the higher test-

retest reliability and greater power and stability of pa- 0.15 0.62 0.36 0.59 0.39 0.70 0.42 0.76 0.25 0.70

rameter estimates associated with adding of informa- AS ES AS ES AS ES AS ES AS ES

tion on irrational fears, we included these along with
phobias in our multivariate analyses. The best-fit model
contained 3 common factors (reflecting genetic and shared
and unique environments) that influenced liability to all
forms of phobia. In addition, each phobic subtype had
evidence of genetic and unique environmental factors spe-
cific to that phobia.
The pattern of results we obtained was similar to that
in our previous multivariate analysis in women (which
contained only 4 phobia subtypes)15 in 2 important ways.
In both sexes, certain genetic factors influenced risk for
all phobia subtypes, whereas others specifically influ-
enced risk for individual phobic subtypes. In both sexes,
the loadings of AnP on this common genetic factor were
higher than those for the other typical phobias of AgP,
SoP, and SiP. We also saw evidence that in men and
women, certain individual environmental experiences in-
creased risk nonspecifically for all phobic subtypes,
whereas others were phobia-subtype specific in their im-
pact. However, 2 differences are noteworthy. First, we
found evidence in our multivariate analysis in men but
not in women of shared environmental effects that had
Results from the best-fitting multivariate genetic model for the subtypes of
phobias (model 6). A indicates additive genetic; C, common or shared family
environment; E, individual specific environmental effects; subscript C, phobia
common factors; and subscript S, additive genetic and individual-specific
environmental effects specific to each phobic subtype. Thus, AC refers to the
additive genetic common factor (additive genes that influence liability to all
phobia subtypes); CC, the shared environmental common factor; and ES,
individual-specific environmental experiences that uniquely influence liability
only to 1 phobia subtype. The magnitude of each path, as estimated using
model 6, is shown. Squaring these path or standardized partial regression
coefficients gives the proportion of variance in the observed variable
accounted for by the latent factor.
a significant impact on AgP and SoP. These results sug-
gest that twin siblings shared some environmental ex-
periences in their family or community that influence risk
specifically for AgP and SoP. Second, the pattern of load-
ings for phobia-specific genetic factors differed between
the sexes. For example, we found in women much larger
contributions of phobia-specific genetic influences for AgP
than AnP, whereas in men the findings were reversed.
Further research will be required to determine if these

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 Table 8. Sources of Variance in Liability to Individual Phobia Subtypes From Best-Fit Fear/Phobia Multivariate Model
Genetic
Shared Environment,
Fear/Phobia Common Specific Total
Agoraphobia 0.11 0.02 0.13
Social 0.05 0.13 0.18
Animal 0.21 0.15 0.36
Situational 0.13 0.18 0.31
Blood/injury 0.22 0.06 0.28
and other differences seen in both sexes are substantive
in nature or due to stochastic fluctuations in patterns of
phobia resemblances in twin pairs.
Our multivariate analyses also permitted us to evalu-
ate the hypothesis that the genetic risk factors for BiP are
distinct from those for the more typical phobia sub-
types. Our results were inconsistent with this hypoth-
esis. Indeed, BiP had the highest loading on the com-
mon genetic factor, and we could not set that path to 0
without a substantial deterioration in fit. The more typi-
cal phobias and BiP probably share common early fear
pathways that then diverge in their outflow to the hy-
pothalamus and autonomic pathways.31 These findings
suggest that genetic risk factors for phobias in men act
largely on the individual differences in the sensitivity of
those early fear pathways shared by BiP and the more typi-
cal phobias.
These analyses should be considered in the context
of 2 potential methodological limitations. First, our cri-
teria for phobias differ from those proposed in recent DSM
editions.32,33 For example, our interviewer-based assess-
ment of impairment, although more objective, may pro-
duce a lower threshold for interference than the self-
report measure used in the DIS. Our definition may also
be broader than that proposed in DSM-III-R criteria32 in
that we require objective impact on respondent behav-
ior rather than the significant interference with normal
routine in DSM-III-R. However, DSM-III-R would in-
clude an unreasonable fear that produced marked dis-
tress, whereas we did not. The Epidemiological Catch-
ment Area screened for a more limited number of phobic
stimuli (14 specific fears) and produced a lifetime preva-
lence for any phobia in men of 10.4%,30 about half of what
we found in this study. By contrast, compared with our
results, the National Comorbidity Study found much
higher rates of SoP in men (11.1%)34 and slightly lower
rates of AgP (3.5%).
Second, a lifetime history of irrational fears and pho-
bias was assessed in this study at a single point in time.
If uncorrelated in twin pairs, unreliability of measure-
ment is indistinguishable from the effects of true indi-
vidual specific environment in our twin models. Our
short-term retest reliability found most tetrachoric cor-
relations for fears and phobias ranging from 0.60 to 0.85.
These results suggest that a substantial proportion of what
we call E in our models in fact represents unreliability
of measurement. If our twin models were corrected for
this effect, as shown in the female sample,17 the esti-
mates of the heritability of liability to phobias (ie, the ge-
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Unique Environment
Common Common Specific Total
0.23 0.25 0.39 0.64
0.05 0.42 0.35 0.77
0.00 0.15 0.49 0.64
0.00 0.12 0.57 0.69
0.01 0.21 0.50 0.71
netic proportion of reliable variance) would be consid-
erably higher than those reported herein.
Accepted for publication October 10, 2000.
This work was supported by grants MH/AA-49492 and
MH-54150 and Research Scientist awards MH-01277 (Dr
Kendler) and MH-01458 (Dr Neale) from the National In-
stitutes of Health, Bethesda, Md. We acknowledge the con-
tribution of the Virginia Twin Registry, now part of the Mid-
Atlantic Twin Registry, to ascertainment of subjects for this
study. The Mid-Atlantic Twin Registry, directed by Linda
Corey, PhD, and Lenn Murrelle, PhD, has received support
from the National Institutes of Health, the Carman Trust
(Richmond, Va), and the WM Keck (Los Angeles, Calif),
John Templeton (Radnor, Pa), and Robert Wood Johnson
(Princeton, NJ) Foundations.
These data were collected under the direction of Patsy
Waring, Sarah Woltz, MA, and Frank Butera, MS.
Corresponding author and reprints: Kenneth S. Ken-
dler, MD, Department of Psychiatry, Medical College of Vir-
ginia of Virginia Commonwealth University, 800 E Leigh
St, PO Box 980126, Richmond, VA 23298-0126.
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